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Case 291 - Discussion

Uploaded: 2009-06-23, Updated: 2009-07-02



Iron stain

Reticulin stain

Trichrome stain

Trichrome stain


Trichrome stain



Usual Interstitial Pneumonia

(Idiopathic Pulmonary Fibrosis/Cryptogenic Fibrosing Alveolitis)

The Key Features

  • §Unknown causes, need to rule out any known causes.

  • Short duration, 2-3 years.

  • Gross: cobblestone, patchy, subpleural and paraseptal.

  • Micro: patchy, dense collagen scar, myofibroblasts or smooth muscle proliferation, and honeycombing. Secondary vascular changes: intimal fibrosis and medial thickening.

  • Definition

    • Diffuse, bilateral interstitial lung disease

    • Often distributed along subpleural and paraseptal regions

    • Characteristic patchy, heterogeneous fibrosis with dense fibrotic scars and scattered fibroblastic foci at the edges, remodeling of the lung and microscopic honeycombing.

    • As an idiopathic clinicopathologic syndrome, UIP = IPF.

    • Histologically, IPF = UIP of unknown causes (excluded drug toxicity, environmental exposures, and collagen vascular diseases

  • Clinical Features

    • Incidence, 7.4 - 10.7 / 100,000

    • Often 50 - 70 years of age, ~ 2/3 > 60 years

    • Etiology: unknown

      • No association with geographic distribution, race or ethnicity.

      • No clear evidence of smoking or viral exposure.

      • Rare familial cases reported.

    • Symptoms: insidious onset of breathlessness with exertion and a nonproductive cough. Occasionally weight loss, fever, fatigue, myalgias, or arthralgias

  • Physical examination

    • Mostly tachypneic with rapid shallow breaths.

    • Bibasilar, late inspiratory, fine crackles.

    • Clubbing in 40 – 75% of patients, often a late finding.

    • Cardiac examination usually normal initially, but later stage with findings of pulmonary hypertension and cor pulmonale.

    • PFT: restriction and impairment of gas exchange. Reduced lung volumes (TLC, FRC, and RV) and compliance. Reduced DLCO.

  • Image Studies

    • CXR:

      • Typically bilateral, symmetric, irregular linear opacities in a reticular pattern.

      • Ground-glass opacities, honeycombing, and decreased lung volumes.

      • Diffuse but mainly the lower lobe in 80% cases.

    • CT: Characteristic irregular lines (reticular pattern) and honeycombing involving mainly the subpleural lung regions.

  • Gross Findings

    • Overall lung size, usually small.

    • Cobblestone appearance of pleural surface due to retraction of scars along the interlobular septa.

    • Cut surface

      • Typically diffuse fibrosis with lower lobe predominance.

      • Distinctive distribution in the subpleural regions and along the interlobular septa.

      • Fibrosis: patchy, mixed with relatively normal lung; firm, rubbery, white connective tissue, honeycomb cystic changes.

  • Histological Features

    • Hallmark: patchy interstitial fibrosis, subpleural and/or paraseptal, alternating with areas of normal lung.

    • Two major types of fibrosis: 1) dense scarring and honeycombing, rich in collagen; 2) fibroblastic foci, contains myofibroblasts or smooth muscle proliferation, when severe “muscular cirrhosis of the lung”.

    • Secondary vascular changes: intimal fibrosis and medial thickening.

    • Lung carcinomas of all histological types develop in 13-31% IPF.



Drug-Induced Lung Disease
Environmental and Occupational Exposures 
    Hypersensitivity pneumonitis
Idiopathic Interstitial Pneumonias
    Idiopathic pulmonary fibrosis/usual interstitial pneumonia
    Nonspecific interstitial pneumonia
    Cryptogenic organizing pneumonia (idiopathic bronchiolitis obliterans organizing pneumonia)     
    Acute interstitial pneumonia
    Respiratory bronchiolitis-interstitial lung disease
    Desquamative interstitial pneumonia
    Lymphocytic interstitial pneumonia
Diffuse Alveolar Damage
Collagen Vascular Disease and Inflammatory Bowel Disease
Primary or Unclassified
    Langerhans’ cell histiocytosis (histiocytosis X)
    Eosinophilic pneumonia
    Pulmonary alveolar proteinosis
    Diffuse alveolar hemorrhage
    Pulmonary aspiration 
    Alveolar microlithiasis
    Pulmonary vasculitis


  • AFIP, Non-Neoplastic Disorders of the Lower Respiratory Tract, series 4;